Study On The One-pot Synthesis Of Nitrogen-containing Heterocycles Based On PDF Conversion

Nitrogen-containing heterocycles are important organic compounds. They have a lot of important applications in biochemistry, medicine, pesticide, dye, perfume, flame retardant materials, conductive materials, photographic materials and many other fields. One-pot synthesis is a very important organic synthetic method, because of the resource-saving and environmental friendly. Our group has systematicly studied the PDF conversion of o-aminonitriles and carbonyl compounds. In order to expand the application of PDF conversion, this doctoral dissertation studies the follow aspects: one was the reset of the functional groups of cyano, aldehyde and carbon anion and their PDF conversion. Another one was the functional groups of cyano, aldehyde and carbon anion were recombined, and three-component one-pot synthesis of nitrogen-containing heterocycles based on PDF conversion was studied. The specific contents are as follows:Firstly, the study of one-pot synthesis of isoindolinone derivativesWe envisaged CoCl2?6H2O-promoted tandem reaction of 2-cyanobenzaldehyde with 1,3-dicarbonyl compounds to provide a convenient synthesis of 3-substitued isoindolinone derivatives. The substrate scope for this processes were explored and a series of isoindolinone derivatives were synthesized. The structure of product 2.3a was confirmed by X-ray crystallographic determine. The possible reaction mechanism for the synthesis of 3-substitued isoindolinones from the 2-cyanobenzaldehyde was proposed, and the carbon anion in place of amino group was involved in the PDF conversion for the synthesis of isoindolinone derivatives.Secondly, the study of one-pot synthesis of pyrimidopyrimidinone derivativesA highly efficient synthesis of pyrimidopyrimidinone derivatives through the NHC-PPIm catalyzed three-component one-pot reaction of 2-(ethoxymethylene) malononitrile, guanidines/amidines and carbonyl compounds was studied. And a normal PDF conversion was combined into this three-component methodology. Carbonyl compounds included chain aliphatic ketones, aliphatic cyclic ketone, aromatic ketones and aromatic aldehydes. All products were characterized by IR, 1H NMR, 13 C NMR, ESI spectra and elemental analysis. We successfully separated corresponding o-aminonitriles which could be transformed to pyrimidopyrimidinone derivatives. Based on that information, a possible reaction mechanism was envisioned. We also studied the change role of intermediate and product through HPLC.Thirdly, the study of one-pot synthesis of pyrazolopyrimidinone derivativesThe convenient synthesis of pyrazolopyrimidinone derivatives by the NaOH-catalysed three-component one-pot(including PDF conversion) transformation of methylenemalononitriles, hydrazines and carbonyl compounds was researched. The main methylenemalononitriles was 2-(ethoxymethylene)malononitrile, hydrazines involved aliphatic hydrazines and aromatic hydrazines. Carbonyl compounds contain aromatic aldehydes and ketones. All products were characterized by IR, 1H NMR, 13 C NMR and ESI spectra. The structure of product 4.4n was confirmed by X-ray crystallographic determine. The key intermediates, 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile, was separated and reacted with benzaldehyde in the catalyst of NaOH to give the targeted product. Then a possible reaction mechanism was depicted.Fourthly, the study of one-pot synthesis of pyrazolopyrimidine derivativesWhen we studied the synthesis of pyrazolopyrimidinone derivatives, we accidentally discovered that alcohol was used not only as soluent, but also as a reactant. So an efficient one-pot synthesis of pyrazolopyrimidine derivatives by the four-component tendem reaction of hydrazines, methylenemalononitriles, aldehydes and alcohols was developed. All products were characterized by IR, 1H NMR, 13 C NMR and HRMS spectra. The structure of product 5.5g was confirmed by X-ray crystallographic determine. We successfully separated three intermediates, and all of them could be transformed to the aimed pyrazolopyrimidine under the same conditions. With those results in hand, two possible reaction mechanisms were proposedFifthly, the study on the synthesis sildenafil based on PDF conversionBased on the one-pot synthesis of pyrazolopyrimidinone derivatives, we studied the modified synthesis of sildenafil based on PDF conversion. 4-Amino-1-methyl-3-propyl-1H-pyrazole-5-carbonitrile was obtained from 2-pentanone through seven steps and reacted with the relative aldehyde to provide sildenafil. This method avoids to use the complicated reagents and saves the reaction steps. All products were characterized by IR, 1H NMR, 13 C NMR and ESI spectra. The key steps of the reactions were optimized. The key intermediate of nitro reducted was obtained and confirmed by NMR and HRMS.